Pathological left ventricular hypertrophy (LVH) in aortic banded animals progresses to congestive heart failure with increased probability of lethal arrhythmias. Changes in cardiac sympathetic innervation accompany pressure-overload LVH, and may contribute to its morbidity. Sympathetic nerve degeneration develops as this condition progresses to failure. The current project will compare sympathetic denervation in hemodynamically compensated and non-compensated pressure-overload LVH in Guinea pigs with suprarenal abdominal aortic constriction. Heart performance, density of immunostained sympathetic nerve fibers, and relative abundances of sympathetic nerve fiber components, determined by radioisotope immunoblotting will be measured. Secondly, the expression of protein markers indicative of glial cell reaction to nerve fiber degeneration will be determined. Levels of glial proteins, S-100A and glial fibrillary acidic protein and GAP-43, a growth-associated protein of regenerating axons will be quantified by immunohistochemistry and immunoassay. The changes in sympathetic neurons accompanying hypertrophy-induced nerve degeneration will be determined by examining stellate sympathetic ganglia during compensated and non-compensated LVH for signs of neuronal atrophy and cell loss, heat shock protein expression and apoptotic cell death. Lastly, the possibility that hypertrophy-induced denervation results from diminished neurotrophic support will be examined by quantifying changes in nerve growth factor production.